Auto-injector

ABSTRACT

An auto-injector for administering a dose of a liquid medicament is presented that has a tubular chassis telescopable in a tubular case, a carrier subassembly comprising a tubular carrier slidably arranged relative to the chassis inside the case, where the carrier adapted to contain a syringe with a hollow injection needle. The injector has a drive spring and a plunger for forwarding load of the drive spring to a stopper of the syringe, wherein the syringe is lockable for joint axial translation with the carrier. There is also a trigger button arranged distally or laterally in or on the case, a control spring arranged around the carrier, and a needle extension control mechanism for coupling a proximal end of the control spring to either the carrier for advancing it for needle extension or to the chassis for needle retraction depending on the relative axial position of the carrier and the chassis.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a U.S. National Phase Application pursuant to35 U.S.C. §371 of International Application No. PCT/EP2012/052640 filedFeb. 16, 2012, which claims priority to European Patent Application No.11155032.3 filed Feb. 18, 2011 and U.S. Provisional Application No.61/445,610 filed Feb. 23, 2011. The entire disclosure contents of theseapplications are herewith incorporated by reference into the presentapplication.

TECHNICAL FIELD

The invention relates to an auto-injector for administering a dose of aliquid medicament.

BACKGROUND

Administering an injection is a process which presents a number of risksand challenges for users and healthcare professionals, both mental andphysical.

Injection devices (i.e. devices capable of delivering medicaments from amedication container) typically fall into two categories—manual devicesand auto-injectors.

In a manual device—the user must provide the mechanical energy to drivethe fluid through the needle. This is typically done by some form ofbutton/plunger that has to be continuously pressed by the user duringthe injection. There are numerous disadvantages to the user from thisapproach. If the user stops pressing the button/plunger then theinjection will also stop. This means that the user can deliver anunderdose if the device is not used properly (i.e. the plunger is notfully pressed to its end position). Injection forces may be too high forthe user, in particular if the patient is elderly or has dexterityproblems.

The extension of the button/plunger may be too great. Thus it can beinconvenient for the user to reach a fully extended button. Thecombination of injection force and button extension can causetrembling/shaking of the hand which in turn increases discomfort as theinserted needle moves.

Auto-injector devices aim to make self-administration of injectedtherapies easier for patients. Current therapies delivered by means ofself-administered injections include drugs for diabetes (both insulinand newer GLP-1 class drugs), migraine, hormone therapies,anticoagulants etc.

Auto-injectors are devices which completely or partially replaceactivities involved in parenteral drug delivery from standard syringes.These activities may include removal of a protective syringe cap,insertion of a needle into a patient's skin, injection of themedicament, removal of the needle, shielding of the needle andpreventing reuse of the device. This overcomes many of the disadvantagesof manual devices. Injection forces/button extension, hand-shaking andthe likelihood of delivering an incomplete dose are reduced. Triggeringmay be performed by numerous means, for example a trigger button or theaction of the needle reaching its injection depth. In some devices theenergy to deliver the fluid is provided by a spring.

US 2002/0095120 A1 discloses an automatic injection device whichautomatically injects a pre-measured quantity of fluid medicine when atension spring is released. The tension spring moves an ampoule and theinjection needle from a storage position to a deployed position when itis released. The content of the ampoule is thereafter expelled by thetension spring forcing a piston forward inside the ampoule. After thefluid medicine has been injected, torsion stored in the tension springis released and the injection needle is automatically retracted back toits original storage position.

High viscosity medicaments require high forces for expelling themthrough the relatively thin injection needle. To achieve these forcesstrong drive springs are needed. This can lead to a high impact felt bythe user when inserting the needle into the skin and to high forces feltby the user when triggering the injection.

SUMMARY

It is an object of the present invention to provide an improvedauto-injector and an improved method for operating an auto-injector.

The object is achieved by an auto-injector according to claim 1 and by amethod according to claim 13.

Preferred embodiments of the invention are given in the dependentclaims.

In the context of this specification the term proximal refers to thedirection pointing towards the patient during an injection while theterm distal refers to the opposite direction pointing away from thepatient. The term inwards refers to a radial direction pointing towardsa longitudinal axis of the auto-injector whereas the term outwardsrefers to the opposite direction radially pointing away from thelongitudinal axis.

According to the invention an auto-injector for administering a dose ofa liquid medicament comprises:

-   -   a tubular chassis telescopable in a tubular case,    -   a carrier subassembly comprising a tubular carrier slidably        arranged relative to the chassis inside the case, the carrier        adapted to contain a syringe with a hollow injection needle, a        drive spring and a plunger for forwarding load of the drive        spring to a stopper of the syringe, wherein the syringe is        lockable for joint axial translation with the carrier,    -   a trigger button arranged distally or laterally in or on the        case,    -   a control spring arranged around the carrier,    -   a needle extension control mechanism for coupling a proximal end        of the control spring to either the carrier for advancing it for        needle extension or to the chassis for needle retraction        depending on the relative axial position of the carrier and the        chassis,    -   a plunger release mechanism arranged for releasing the plunger        when the carrier has at least almost reached a extended proximal        position,    -   a detent mechanism arranged for coupling the chassis to the        carrier for joint axial translation relative to the case,        wherein the detent mechanism is arranged to decouple the chassis        from the carrier upon actuation of the trigger button thus        allowing the carrier to move relative to the chassis so as to        cause the needle extension control mechanism to switch the        proximal end of the control spring to the carrier for needle        extension,    -   a syringe retraction control mechanism arranged for coupling a        distal end of the control spring to either the carrier for        needle refraction or to the case otherwise.

The carrier subassembly with the integrated drive spring allows foremploying a strong drive spring without any impact on the user whentriggering the auto-injector or during needle extension since theseactions are achieved or opposed by the control spring which can bespecified considerably weaker than the drive spring. This allows fordelivering highly viscous medicaments.

There are a number of significant benefits of separating the functionsbetween the drive spring and the control spring in this way. Theauto-injector is always needle safe, i.e. the needle can be retractedbefore the injection is complete. The reliability of the auto-injectoris improved as the components for needle advance and retraction are notloaded by the high impact of a freely expanding high force drive spring.The auto-injector is well suited to serve as a platform as the drivespring can be swapped to deliver different viscosity drugs withoutaffecting the insertion or retraction functions. This is particularlyadvantageous for high viscosity fluids.

Releasing the drive spring upon the needle reaching an advanced proximalposition, e.g. when the needle is advanced to a corresponding injectiondepth, avoids a so called wet injection, i.e. medicament leaking out ofthe needle which is a problem in conventional art auto-injectors, whereboth needle extension and injection are achieved by pushing on thestopper. The auto-injector according to the invention solves the wetinjection problem by the separate springs for translation of the carrierand for drug delivery.

The auto-injector according to the invention has a particularly low partcount compared to most conventional auto-injectors thus reducingmanufacturing costs. The arrangement with separate control spring anddrive spring for fluid injection allows for using one design fordifferent viscosity liquids by just changing the drive spring, and fordifferent volumes just by changing the length of the plunger. This is anadvantage over conventional art designs where the main spring alsopowers needle extension and/or retraction.

In the context of this specification the chassis is generally consideredas being fixed in position so motion of other components is describedrelative to the chassis.

In an initial as delivered state of the auto-injector the proximal endof the control spring is coupled to the chassis by the needle extensioncontrol mechanism while the distal end is coupled to the case by thesyringe retraction control mechanism, release of the drive spring isprevented by the plunger release mechanism, decoupling of the chassisfrom the carrier is prevented by the detent mechanism.

In order to trigger the auto-injector the case has to be translated inthe proximal direction relative to the chassis against the force of thecontrol spring. When the case has at least almost reached an advancedproximal position the detent mechanism is unlocked thereby allowingtranslation of the carrier relative to the chassis. Preferably thisposition has been reached, when the case has moved 85%-98% of its totalproximal extension. The relative translation of the case and the chassiscould be achieved, e.g. by fixing the chassis and moving the case. Forthe purpose of injection, e.g., the chassis may be fixed by pressingagainst an injection site, e.g. a patient's skin. Hence a user, e.g. thepatient or a caregiver, could grab the case with their whole hand andpush the chassis protruding from the proximal end against the injectionsite, thereby translating the case relative to the chassis in proximaldirection and triggering the auto-injector in a way described above.

The carrier now is unlocked to be translated in the proximal direction.As the carrier translates in the proximal direction relative to the caseand to the chassis it thereby switches the needle extension controlmechanism depending on the relative position of the carrier in thechassis so as to decouple the proximal end of the control spring fromthe chassis and couple it to the carrier, thereby releasing the controlspring for advancing the carrier for needle extension. For the purposeof injection, e.g., the user could manually depress a trigger buttoncoupled to the carrier forcing the carrier in the proximal direction.This would cause the needle to be extended according to the needleextension control mechanism described before. Again, for purpose ofinjection, the user pushing the injector against an injection site couldpress the trigger button thereby translating the carrier in the proximaldirection relative to the case and the chassis thereby switching theneedle extension control mechanism as described before. Advancing thecarrier under the force of the control spring would then result inadvancing the needle into the skin.

Alternatively the control spring could initially be coupled to thecarrier by the needle extension control mechanism so that the carrierwould be immediately advanced when the detent mechanism is unlocked bytranslation of the case into the advanced position.

As the needle translates with the carrier subassembly to an extendedproximal position, where it is no longer needle safe, the drive springis released by the plunger release mechanism thereby allowing the drivespring to advance the plunger and the stopper for at least partiallyexpelling the medicament. This release of the drive spring is preferablytriggered by the carrier reaching a predefined relative position withinthe case. This position is reached, when the carrier has at least almostreached the extended proximal position. Preferably, this position is at85% to 98% proximal extension. If, for example, the extension length is1 cm the position would fall into the range of 8.5 mm-9.8 mm proximalextension length

For the purpose of injection the extended proximal position maycorrespond to an intended injection depth. Hence the drive spring couldbe released by the plunger release mechanism once the injection depth issubstantially reached thereby allowing the drive spring to advance theplunger and the stopper for at least partially delivering themedicament.

If the auto-injector is removed from the injection site after thestopper has bottomed out in the syringe or at any point duringinjection, the case is translated in the distal direction under load ofthe control spring relative to the carrier subassembly.

The needle retraction is triggered by moving the case in distaldirection relative to the chassis and the carrier under the force of thecontrol spring. As the case reaches a defined position relative to thecarrier the proximal end of the control spring is decoupled from thecarrier and coupled to the chassis by the needle extension controlmechanism. Furthermore the distal end of the control spring is decoupledfrom the trigger sleeve and coupled to the carrier by the syringeretraction control mechanism. The sequencing of this switching iscritical as retraction will fail if both collars are attached to thecarrier at the same time. This is overcome by separating the switchingof the collars by a significant displacement of the case, which providesfor first switching the needle extension control mechanism and then thesyringe retraction control mechanism, e.g.

As the control spring now pushes against the chassis in the proximaldirection and against the carrier in the distal direction the carriersubassembly is retracted into the chassis into a needle safe position bythe control spring, where the proximal end of the needle is covered. Asthis retraction is triggered by the relative position between case,chassis, and carrier, it is particularly independent from expelling themedicament. For the purpose of injection this position of the caserelative to the carrier could be reached, e.g. if the auto-injector isremoved from the injection site. When, e.g., the user still grabbing thecase with their whole hand and pushing the chassis protruding from theproximal end against the injection site move their hand in distaldirection, the case will be moved in distal direction relative to thecarrier and the chassis and the mechanism will be triggered as describedbefore. The needle will thus be retracted from the injection site underthe force of the control spring.

According to one embodiment the needle extension control mechanism maycomprise a first collar biased by the control spring in the proximaldirection, wherein at least one resilient beam is proximally arranged onthe first collar, wherein respective recesses are arranged in thecarrier and case, wherein a transversal extension of a head of theresilient beam is wider than a gap between the carrier and the chassiscausing the head of the resilient beam to abut a distal face on therecess in the chassis while being prevented from deflecting in an inwarddirection by the carrier or to abut a distal face on the recess in thecarrier while being prevented from deflecting in an outward direction bythe chassis thereby forwarding load from the control spring to thecarrier for needle extension, wherein the resilient beam is arranged tobe switched between the chassis and the carrier by ramped engagement ofthe head to the distal faces under load of the control spring dependingon the relative longitudinal position between the chassis and thecarrier. As the head of the resilient beam may be inwardly and outwardlyramped it may be referred to as an arrowhead.

The plunger release mechanism may comprise at least one resilient arm onthe carrier arranged to be in a ramped engagement to the plunger so asto disengage them under load of the drive spring, wherein a pegprotrudes from a distal end face of the trigger button in the proximaldirection in a manner to support the resilient arm preventingdisengagement of the carrier from the plunger and thus release of thedrive spring when the carrier is in a distal position. The triggerbutton is arranged to remain in position relative to the case when thecarrier is translated for advancing the needle. That means, the triggerbutton, initially coupled to the carrier, pushes the carrier in theproximal direction when depressed. As soon as the control spring takesover further advancing the carrier the trigger button may abut the caseand decouple from the carrier, staying in position as the carrier moveson. Hence the resilient arm is pulled away from the peg thus allowingdeflection of the resilient arm due to the ramped engagement under loadof the drive spring for disengaging the plunger from the carrier andreleasing the drive spring for drug delivery when the carrier hasreached a predefined position during needle advancement.

The detent mechanism may be arranged to provide a resistive force whichhas to be overcome to advance the carrier in the proximal direction forneedle extension. The carrier may be coupled to a trigger button and theforce pushing the trigger button has to exceed the resistive force ofthe detent mechanism. E.g., once the user applies a force on the triggerbutton which exceeds a pre-determined value the detent mechanismreleases, initiating the injection cycle. If the pre-determined value isnot overcome the detent mechanism pushes the carrier and trigger buttonback into their prior position. This ensures that the auto-injector isalways in a defined state, either triggered or not triggered, not halftriggered by the user hesitating.

The detent mechanism may also be arranged to provide a resistive forceresisting translation of the carrier in the distal direction relative tothe chassis for keeping the carrier in a defined position in atransitional state with both ends of the control spring decoupled fromthe carrier. This transitional state may be required for retracting theneedle on removal from the injection site. As the carrier is biasedagainst the injection site by the control spring before removal from theinjection site it has to be decoupled from the proximal end of thecontrol spring and coupled to the distal end for retraction. Thesequencing of this switching is critical as retraction will fail if bothends of the control spring are attached to the carrier at the same time.This is overcome by separating the switching of the ends by asignificant displacement of the case, which moves in the distaldirection relative to the chassis on removal of the injection site underload of the control spring. As the switching of the distal end of thecontrol spring to the carrier depends on the relative position of thecase to the carrier the carrier has to be fixed in the transitionalstate which is achieved by the detent mechanism.

In one embodiment the detent mechanism comprises a resilient beam on thechassis and a rhomboid ramp member on the carrier, the resilient beambeing essentially straight when relaxed and having a first beam headarranged to interact in a ramped engagement with a proximal fourth rampor a distal fifth ramp on the rhomboid ramp member in such a manner thatapplication of a translative force on the carrier relative to thechassis in the proximal direction with the first beam head engaged tothe fourth ramp deflects the resilient beam in one transversaldirection, e.g. outwards when a predetermined value of the translativeforce, at least depending on the resilience of the resilient beam, isovercome so as to allow the first beam head to travel along onetransversal side of the rhomboid ramp member on continued relativetranslation of the components. The beam head may protrude transversallyfrom the resilient beam in a manner to distort the resilient beam bylever action when pushed against the rhomboid ramp member thereby alsodefining the predetermined value of the translative force to be overcomeby the carrier. Furthermore, the contacting faces of the first beam headand the rhomboid ramp member may have their friction adapted to definethe required force by appropriately choosing their shape and materialproperties. The resilient beam is allowed to relax when the first beamhead has reached the fifth ramp thereby engaging it in a manner thatapplication of a translative force on the carrier in the distaldirection deflects the resilient beam in the other transversaldirection, e.g. inwards when a predetermined value of the translativeforce, at least depending on the resilience of the resilient beam, isovercome so as to allow the first beam head to travel along the othertransversal side of the rhomboid ramp member on continued translation ofthe carrier. The first beam head may also be allowed to relax behind thefourth ramp at the end of this motion for preventing the carrier frombeing advanced again, e.g. when the auto-injector is being heavilyshaken after use.

It goes without saying that the positions of the resilient beam on thechassis and the rhomboid ramp member on the carrier may be switchedwithout altering the function of the detent mechanism.

When the auto-injector or the syringe is assembled a protective needlesheath may be attached to the needle for keeping the needle sterile andpreventing both, damage to the needle during assembly and handling andaccess of a user to the needle for avoiding finger stick injuries.Removal of the protective needle sheath prior to an injection usuallyrequires a relatively high force for pulling the protective needlesheath off the needle and needle hub in the proximal direction. In orderto maintain pre injection needle safety and prevent exposure of theneedle translation of the syringe in the proximal direction due to thisforce has to be avoided. For this purpose the case may be arranged tolock the detent mechanism prior to being translated in the proximaldirection relative to the chassis when the chassis is being pressedagainst the injection site so as to avoid translation of the carrier.This may be achieved by a rib in the case preventing deflection of theresilient beam of the detent mechanism by supporting it outwardly.Translation of the case is translated into the advanced position in theproximal direction on contact to the injection site is arranged tounlock the detent mechanism rendering it operable. This may be achievedby the rib being moved with the case so as to no longer outwardlysupporting the resilient beam of the detent mechanism. In order toensure that the case is not moved in the proximal direction unlockingthe detent mechanism before the protective needle sheath is removed acap may be attached to the proximal end of the case so as to make thechassis inaccessible before the cap is removed. The cap preferablyengages the protective needle sheath by means of a barb in a manner toremove the protective needle sheath when the cap is being pulled off theauto-injector. In order to facilitate removal of the cap it may have aprofiled surface mating with a surface on the case so that the cap ispulled off when rotated. The barb may be connected to the cap in amanner allowing them to rotate independently so as to avoid torque onthe protective needle sheath when the cap is rotated in order not todistort the needle inside the protective needle sheath.

The distally arranged trigger button may be at least initially coupledto the carrier, wherein the case is arranged to abut the trigger buttonin the initial state preventing depression of the trigger button. Ontranslation of the case into the advanced position when the chassis isbeing pressed against the injection site the trigger button remainscoupled to the carrier thus emerging from the case which has been movedrelative to the chassis, carrier and trigger button so as to allowdepression of the trigger button for starting an injection cycle. Thus asequence of operation is defined for the auto-injector to be actuated,first pressing it against the injection site and then to push thetrigger button. This reduces the risk of finger stick injuriesparticularly if the user were to be confused which end of theauto-injector to apply against their skin. Without a sequence the userwould risk inserting the needle into their thumb which is significantlyless probable with the forced sequence.

The syringe retraction control mechanism may comprise a second collarbearing against the distal end of the control spring and having aresilient proximal beam with a second beam head having an inward boss.The second beam head is arranged to be in a ramped engagement with asecond case detent in the case in a manner ramping the second beam headin the inward direction under load of the control spring in the distaldirection. The inward boss is arranged to inwardly abut the carrier forpreventing inward deflection of the second beam head and keep the secondcollar locked to the case. A third recess is arranged in the carrier forallowing the inward boss to be inwardly deflected on translation of thecase in the distal direction relative to the carrier on removal of theauto-injector from the injection site.

In an alternative embodiment the first collar and/or the second collarmay also be threaded to one of the components which they are intended tocouple to the control spring wherein the case would be arranged toprevent the threads from decoupling in some relative longitudinalpositions while allowing the collar to rotate out of the threadedengagement in other relative longitudinal positions so as to allow thecollars to switch to the respective other component to be coupled to thecontrol spring.

In an alternative embodiment the trigger button may be arrangeddistally, wherein the case is arranged as a wrap-over sleeve triggerhaving a closed distal end face covering the trigger button. In aninitial state a clearance is provided between the distal end face of thesleeve trigger and the trigger button allowing for some travel of thesleeve trigger against the bias of the control spring in the proximaldirection in a first phase before abutting the trigger button. As soonas the sleeve trigger has contacted the trigger button the triggerbutton is pushed by the sleeve trigger on further translation in asecond phase. This embodiment allows for keeping the majority of thecomponents of the auto-injector while only the described features needmodification allowing to customize a platform device to particularrequirements. An auto-injector with a sleeve trigger is particularlywell suited for people with dexterity problems since, as opposed toconventional art auto-injectors, triggering does not require operationof small buttons by single fingers. Instead, the whole hand is used.

Retraction of the needle requires the user to lift the auto-injector farenough from the injection site to allow the case or sleeve trigger totranslate back in the distal direction to switch the control spring. Asit may be difficult for the user to know if the injection is finished ornot a releasable feedback component may be provided, capable of, uponrelease, generating an audible and/or tactile feedback to the user,wherein the feedback component is arranged to be released when theplunger reaches a position relative to the syringe in which the stopperis located in proximity of a proximal end of the syringe, i.e. , e.g.,when the injection is at least almost finished. The released feedbackcomponent then impacts on a housing component, such as the case, sleevetrigger or trigger button indicating the end of the injection. Impactinga directly accessible component allows for high perceptibility of thenoise and direct access to the user's hand or finger for generating thetactile feedback. Preferably the feedback component may impact thetrigger button which may be shaped as a drum for providing a loud noise.

The needle extension length or depth is preferably defined by thecarrier relative to the chassis not relative to the case, so if the userflinches or fails to hold the auto-injector hard against the injectionsite, only the case will move in the distal direction while theinjection depth remains constant. As long as this case motion does notexceed a set distance the case does not yet switch the control springfor needle retraction.

The auto-injector may be operated by a number of key mechanicaloperations:

The case is advanced relative to the chassis compressing the controlspring giving the user the impression of depressing a skin interlocksleeve. All other components remain in the same place during caseadvance resulting in the trigger button appearing from the distal end ofthe case.

The user pushes the trigger button which can now be operated. Buttondepression directly moves the carrier and hence the drive sub-assemblyin the proximal direction a set distance until the control spring takesover via the first collar and fully extends the needle, e.g. inserts theneedle into the injection site.

The trigger button stops on the distal end of the case as the carriercontinues translating in the proximal direction. The motion of thecarrier relative to the trigger button is used to release the drivespring just before full insertion depth is reached, e.g. by pulling apeg on the trigger button out of the carrier thus allowing the plungerto move. The drive spring drives the plunger down the syringe barrelexpelling the medicament.

A feedback mechanism is released when the plunger is near the end oftravel shortly before the stopper bottoms out in the syringe, providingaudible and/or tactile indicator of the end of injection to the user.

The needle remains fully extended until the user moves the case back aset distance relative to the chassis at which point the second collardecouples from the case and couples to the carrier while the firstcollar decouples from the carrier and couples to the chassis thusallowing the control spring to retract the carrier and hence the needle.

The auto-injector may preferably be used for subcutaneous orintra-muscular injection, particularly for delivering one of ananalgetic, an anticoagulant, insulin, an insulin derivate, heparin,Lovenox, a vaccine, a growth hormone, a peptide hormone, a proteine,antibodies and complex carbohydrates. The auto-injector may preferablybe adapted to be used for injecting a liquid medicament with highviscosity, e.g. liquid solutions of antibody medicaments.

The term “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, a antibody, an enzyme, anantibody, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exedin-3 or exedin-4 or an analogue or derivative ofexedin-3 or exedin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(w-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-S er-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

-   H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,-   H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,-   des Pro36 [Asp28] Exendin-4(1-39),-   des Pro36 [IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or-   des Pro36 [Asp28] Exendin-4(1-39),-   des Pro36 [IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   wherein the group -Lys6-NH2 may be bound to the C-terminus of the    Exendin-4 derivative;-   or an Exendin-4 derivative of the sequence-   H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,-   des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,-   H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,-   des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,-   H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-Lys6-NH2,-   H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]    Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(S1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2;-   or a pharmaceutically acceptable salt or solvate of any one of the    afore-mentioned Exedin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C 1 -C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17 .ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

The drive spring and control spring may be compression springs. However,they may likewise be any kind of stored energy means such as torsionsprings, gas springs etc.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus, are not limitiveof the present invention, and wherein:

FIG. 1 shows two longitudinal sections of an auto-injector in differentsection planes in a state prior to use,

FIG. 2 shows two longitudinal sections of the auto-injector afterremoval of a cap and a protective needle sheath,

FIG. 3 shows two longitudinal sections of the auto-injector with thecase moved in proximal direction relative to the chassis,

FIG. 4 shows two longitudinal sections of the auto-injector with atrigger button depressed,

FIG. 5 shows two longitudinal sections of the auto-injector duringneedle extension,

FIG. 6 shows two longitudinal sections of the auto-injector with theneedle in extended proximal position,

FIG. 7 shows two longitudinal sections of the auto-injector duringexpelling the medicament,

FIG. 8 shows two longitudinal sections of the auto-injector where thestopper is located in proximity of a proximal end of the syringe,

FIG. 9 shows two longitudinal sections of the auto-injector where thecase is moved in distal direction relative to the chassis,

FIG. 10 shows two longitudinal sections of the auto-injector with theneedle retracted into a needle safe position,

FIG. 11 shows schematic views of a detent mechanism for controllingmovement of a carrier relative to a chassis of the auto-injector in fourdifferent states,

FIG. 12 shows schematic views of a needle extension control mechanismfor controlling movement of a first collar in six different states,

FIG. 13 shows schematic views of a syringe retraction control mechanismin three different states

FIG. 14 shows schematic views of a feedback release mechanism foraudibly and/or tactily indicating the end of injection in threedifferent states,

FIG. 15 shows schematic views of a plunger release mechanism in threedifferent states,

FIG. 16 shows schematic views of a button release mechanism in threedifferent states,

FIG. 17 is an isometric view of an alternative embodiment of the plungerrelease mechanism,

FIG. 18 is a longitudinal section of an alternative embodiment of thebutton release mechanism,

FIG. 19 shows longitudinal sections of an alternative embodiment of thedetent mechanism,

FIG. 20 is a longitudinal section of a third embodiment of the detentmechanism,

FIG. 21 is a longitudinal section of an alternative embodiment of thefeedback release mechanism,

FIG. 22 shows longitudinal sections of an alternative embodiment of theneedle extension control mechanism, also arranged to perform thefunction of the detent mechanism on needle retraction and needleextension,

FIG. 23 is an isometric view of the needle extension control mechanismof FIG. 22,

FIG. 24 shows longitudinal sections of a third embodiment of the needleextension control mechanism, also arranged to perform the functions ofthe detent mechanism,

FIG. 25 is an isometric view of the needle extension control mechanismof FIG. 24,

FIG. 26 shows longitudinal sections of a third embodiment of thefeedback release mechanism, and

FIG. 27 is another embodiment of the auto-injector having a wrap-oversleeve trigger instead of a trigger button.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

A ramped engagement in the terminology of this specification is anengagement between two components with at least one of them having aramp for engaging the other component in such a manner that one of thecomponents is flexed aside when the components are axially pushedagainst each other provided this component is not prevented from flexingaside.

Figures la and lb show two longitudinal sections of an auto-injector 1in different section planes, the different section planes approximately90° rotated to each other, wherein the auto-injector 1 is in an initialstate prior to starting an injection. The auto-injector 1 comprises achassis 2. In the following the chassis 2 is generally considered asbeing fixed in position so motion of other components is describedrelative to the chassis 2. A syringe 3, e.g. a Hypak syringe, with ahollow injection needle 4 is arranged in a proximal part of theauto-injector 1. When the auto-injector 1 or the syringe 3 is assembleda protective needle sheath 5 is attached to the needle 4. A stopper 6 isarranged for sealing the syringe 3 distally and for displacing a liquidmedicament M through the hollow needle 4. The syringe 3 is held in atubular carrier 7 and supported at its proximal end therein. The carrier7 is slidably arranged in the chassis 2.

A drive spring 8 in the shape of a compression spring is arranged in adistal part of the carrier 7. A plunger 9 serves for forwarding theforce of the drive spring 8 to the stopper 6.

The drive spring 8 is loaded between a distal carrier end face 10 of thecarrier 7 and a thrust face 11 arranged distally on the plunger 9.

The carrier 7 is a key element housing the syringe 3, the drive spring 8and the plunger 9, which are the components required to expel themedicament M from the syringe 3. These components can therefore bereferred to as a drive sub-assembly.

The chassis 2 and the carrier 7 are arranged within a tubular case 12. Atrigger button 13 is arranged at a distal end of the case 12. In aplunger release mechanism 27 a peg 14 protrudes from a distal end faceof the trigger button 13 in the proximal direction P between tworesilient arms 15 originating from the distal carrier end face 10 thuspreventing them from flexing towards each other in an initial state Aillustrated in FIG. 15A. In FIG. 15A only one of the resilient arms 15is shown to illustrate the principle. Outwardly the resilient arms 15are caught in respective first recesses 16 in a distal plunger sleeve 17attached distally to the thrust face 11 and arranged inside the drivespring 8. The engagement of the resilient arms 15 in the first recesses16 prevents axial translation of the plunger 9 relative to the carrier7. The resilient arms 15 are ramped in a manner to flex them inwards onrelative motion between the plunger 9 and the carrier 7 under load ofthe drive spring 8, which is prevented by the peg 14 in the initialstate A.

The carrier 7 is locked to the chassis 2 for preventing relativetranslation by a detent mechanism 18 illustrated in more detail in FIGS.11A to 11D.

The trigger button 13 is initially engaged to the case 12 by a buttonrelease mechanism 26 and cannot be depressed. The button releasemechanism 26 is illustrated in detail in FIGS. 16A to 16C. Referring nowto FIG. 16A the button release mechanism 26 comprises a resilientproximal beam 13.1 on the trigger button 13, the proximal beam 13.1having an outward first ramp 13.2 and an inward second ramp 13.3. In aninitial state A illustrated in FIG. 16A the outward first ramp 13.2 isengaged in a ramped first case detent 12.1 preventing the trigger button13 from moving out of the distal end D. The trigger button 13 proximallyabuts both the case 12 and the carrier 7 hence being prevented frombeing depressed in the proximal direction P.

Referring again to FIGS. 1A and 1B a control spring 19 in the shape ofanother compression spring is arranged around the carrier 7 and actsbetween a proximal first collar 20 and a distal second collar 21. Thecontrol spring 19 is used to move the carrier 7 and hence the drivesub-assembly in the proximal direction P for needle extension or in thedistal direction D for needle retraction.

In the state as delivered as shown in FIGS. 1a and 1b a cap 22 isattached to the proximal end of the case 12 and the protective needlesheath 5 is still in place over the needle 4 and the needle hub. Aninner sleeve 22.1 of the cap 22 is arranged inside the chassis 2 andover the protective needle sheath 5. In the inner sleeve 22.1 a barb 23is attached. The barb 23 is engaged to the protective needle sheath 5for joint axial translation.

A sequence of operation of the auto-injector 1 is as follows:

A user pulls the cap 22 from the proximal end of the case 12. The barb23 joins the protective needle sheath 5 to the cap 22. Hence, theprotective needle sheath 5 is also removed on removal of the cap 22.FIGS. 2a and 2b show the auto-injector 1 with the cap 22 and needlesheath 5 removed. The carrier 7 and syringe 3 are prevented from movingin the proximal direction P by the detent mechanism 18 being in a stateA as in FIG. 11A. Referring now to FIG. 11A, the detent mechanism 18comprises a resilient beam 2.1 on the chassis 2 with an inwardlyprotruding first beam head 2.2. The first beam head 2.2 has a proximalthird ramp 2.3. The detent mechanism 18 further comprises a rhomboidramp member 7.1 on the carrier 7 having a proximal fourth ramp 7.2 and adistal fifth ramp 7.3. In state A a rounded off distal side of the firstbeam head 2.2 abuts the ramp member 7.1 in the distal direction Dresisting movement of the carrier 7 in the proximal direction P relativeto the chassis 2. A rib on the case 12 is provided for preventingoutward deflection of the resilient beam 2.1 thereby also preventingmotion of the carrier 7 relative to the chassis 2.

Referring again to FIGS. 2A and 2B the user grabs the case 12 and placesthe chassis 2 protruding from the case 12 at the proximal end P againstan injection site, e.g. a patient's skin. As the auto-injector 1 ispressed against the injection site the case 12 translates in theproximal direction P relative to the chassis 2 into an advanced positionas illustrated in FIGS. 3A and 3B. The second collar 21 is locked to thecase 12 and is moved with the case 12 relative to the chassis 2 andrelative to nearly all other components of the auto-injector 1 thusslightly compressing the control spring 19 against the first collar 20which is prevented from moving in the proximal direction P by thechassis 2 due to a needle extension control mechanism 24 being in astate A illustrated in detail in FIG. 12A. Referring now to FIG. 12A, aresilient member in the shape of an arrowhead 20.1 is proximallyarranged on the first collar 20. The first collar 20 with the arrowhead20.1 is being forced in the proximal direction P under load of thecompressed control spring 19. An outward sixth ramp 20.2 on thearrowhead 20.1 interacts with a second distal seventh ramp 2.4 on thechassis 2 ramping the arrowhead 20.1 in an inward direction I which isprevented by the arrowhead 20.1 inwardly abutting the carrier 7. Hence,the first collar 20 cannot translate in the proximal direction P.

Referring again to FIGS. 3A and 3B the second collar 21 is locked to thecase due to a syringe refraction control mechanism 25 being in a state Aillustrated in detail in FIG. 13A. Referring now to FIG. 13A, thesyringe retraction control mechanism 25 comprises a resilient proximalbeam 21.1 on the second collar 21, the proximal beam 21.1 having asecond beam head 21.2 having an inward boss 21.3 and a distal outwardeighth ramp 21.4. The distal outward eighth ramp 21.4 is engaged in aramped second case detent 12.2 in a manner ramping the second beam head21.1 in the inward direction I with the second collar 21 under load ofthe control spring 19 in the distal direction D which is prevented bythe inward boss 21.3 inwardly abutting the carrier 7.

Referring again to FIGS. 3A and 3B, if the user was to move the case 12away from the injection site, the control spring 19 expands returningthe auto-injector 1 to the initial condition after removal of the cap 22as illustrated in FIGS. 2A and 2B.

In the state as in FIGS. 3A and 3B the carrier 7 continues to beprevented from moving in the proximal direction P by the detentmechanism 18, however with the case 12 in its advanced position thedetent mechanism 18 is unlocked as the rib on the case 12 has also movedand no longer prevents outward deflection of the resilient beam 2.1.Movement of the case 12 relative to the carrier 7, which is locked tothe chassis 2 by the detent mechanism 18, causes the button releasemechanism 26 to switch to a state B illustrated in FIG. 16B. The triggerbutton 13 cannot translate with the case 12 in the proximal direction Pas it is abutted against the carrier 7. The ramp on the first casedetent 12.1 interacts with the outward first ramp 13.2 on the proximalbeam 13.1 on the trigger button 13 deflecting the proximal beam 13.1 inthe inward direction I thus engaging the inward second ramp 13.3 on theproximal beam 13.1 in a ramped carrier detent 7.4 arranged in thecarrier 7. As the case 12 is translated further in the proximaldirection P it supports the proximal beam 13.1 outwardly thus lockingthe trigger button 13 to the carrier 7. The trigger button 13 nowprotrudes from the distal end D of the chassis 12 and is ready to bepressed.

In the state as in FIGS. 3A and 3B the user depresses the trigger button13 in the proximal direction P. As the trigger button 13 abuts againstthe carrier 7 the carrier 7 is pushing in the proximal direction Pagainst the chassis 2, the carrier 7 and the chassis 2 interacting inthe detent mechanism 18. The force exerted by the user pressing thetrigger button 13 is resolved through the chassis 2 onto the injectionsite, not between the trigger button 13 and the case 12. The detentmechanism 18 provides a resistive force when the user pushes the triggerbutton 13. Once the user applies a force which exceeds a pre-determinedvalue the detent mechanism 18 releases, initiating the injection cycle.Referring now to FIG. 11B showing the detent mechanism 18 in a state B,the resilient beam 2.1 on the chassis 2 begins to bow under load fromthe rhomboid ramp member 7.1 on the carrier 7, storing elastic energy.Despite the proximal fourth ramp 7.2 on the ramp member 7.1 frictionbetween the contacting faces of the first beam head 2.2 and the proximalfourth ramp 7.2 prevents movement of the first beam head 2.2 in theoutward direction 0 until the straightening force in the resilientlydeformed beam 2.1 is sufficiently large to overcome it. At this pointthe resilient beam 2.1 is deflected in the outward direction 0 movingout of the way of the carrier 7 thus allowing the carrier 7 to translatein the proximal direction P. When the carrier 7 travels sufficiently farin the proximal direction P the rhomboid ramp member 7.1 on the carrier7 passes under the first beam head 2.2 thus allowing it to relax andmove back in the inward direction I distally behind the rhomboid rampmember 7.1 in a state C illustrated in FIG. 11 C at the same timeconstraining translation of the carrier 7 in the distal direction Drelative to the chassis 2.

Once the carrier 7 slides far enough in the proximal direction Prelative to the first collar 20 the needle extension control mechanism24 is switched to a state B as illustrated in FIG. 12B. In FIG. 12B thecarrier 7 has been translated in the proximal direction P in such amanner that the arrowhead 20.1 on the first collar 20 is no longerinwardly supported. This may be achieved by a second recess 7.5 in thecarrier 7. The arrowhead 20.1 is now deflected in the inward direction Iinto the second recess 7.5 under load of the control spring 19 arrivingat a state C as illustrated in FIG. 12C. The first collar 20 is nowdecoupled from the chassis 2. Instead, the arrowhead 20.1 couples thefirst collar 20 to the carrier 7 by an inward ninth ramp 20.3 engaging adistal tenth ramp 7.6 on the carrier 7 at the proximal end of the secondrecess 7.5. Hence, the control spring 19 continues moving the carrier 7in the proximal direction P from this point. Whilst the user advancesthe needle 4 by a proportion of its travel, the control spring 19 takesover insertion before the needle 4 protrudes from the proximal end P.Therefore the user experience is that of pressing a button, rather thanmanually inserting a needle.

The detent mechanism 18 relies on the user applying a force rather thana displacement. Once the force applied exceeds the force required toswitch the detent the user will push the trigger button 13 fully,ensuring that the first collar 20 will always switch. If the user failsto pass the detent, the trigger button 13 returns to its unused stateready for use as illustrated in FIGS. 3A and 3B. This feature avoids theauto-injector 1 arriving in an undefined state.

FIGS. 4A and 4B show the auto-injector 1 with the trigger button 13depressed sufficiently for the control spring 19 to couple on to thecarrier 7 and continue moving the carrier 7 forwards, but not yetabutting the case 12.

The carrier 7 coupled to the first collar 20 is translated in theproximal direction P driven by the control spring 19. As the syringe 3is arranged for joint axial translation with the carrier 3 the syringe 3and needle 4 are also translated resulting in the needle 4 protrudingfrom the proximal end P and being inserted into the injection site. Thetrigger button 13 returns to its initial position relative to the case12 and latches back to the case 12 from the carrier 7 as in state A inFIG. 16 A. The carrier 7 translates further in the proximal direction Ppreventing inward deflection of the proximal beam 13.1 so the outwardfirst ramp 13.2 cannot disengage from the first case detent 12.1.

Immediately prior to the needle 4 reaching full insertion depth asillustrated in FIGS. 5A and 5B the peg 14 on the trigger button 13 iscompletely pulled out from between the resilient arms 15 on the carrier7. Hence, the plunger release mechanism 27 arrives in a state B shown inFIG. 15B with the resilient arms 15 no longer inwardly supported by thepeg 14. Due to the ramped engagement of the resilient arms 15 in thefirst recess 16 they are deflected in the inward direction I under loadof the drive spring 8 arriving in a state B illustrated in FIG. 15C.

Hence, the plunger 9 is released from the carrier 7 and driven in theproximal direction P by the drive spring 8, ready to expel themedicament M. The force to pull the peg 14 out from between theresilient arms 15 is provided by the control spring 19 while the forcerequired to deflect the resilient arms 15 out of engagement to theplunger 9 is provided by the drive spring 8.

While the plunger 9 moves and closes a gap to the stopper 6 the movementof the carrier 7 in the proximal direction P is completed by the controlspring 19 pushing the first collar 20. As the carrier 7 moves withrespect to the chassis 2 during needle extension the needle extensionmechanism 24 arrives in a state D illustrated in FIG. 12D. The arrowhead20.1 has moved with the carrier 7 and is still kept inwardly deflectedby the chassis 2 thus preventing the first collar 20 from disengagingthe carrier 7. The arrowhead 20.1 must be able to deflect in the outwarddirection O to allow retraction which will be discussed below. In orderto allow outward deflection the arrowhead 20.1 travels proximally beyondthe part of the chassis 2 shown in FIGS. 12A to 12F next to an aperture2.5 in the chassis 2. However, as long as the case 12 is being keptpressed against the injection site and not allowed to return in thedistal direction D beyond a predefined distance under load of thecontrol spring 19 the arrowhead 20.1 will be kept from deflecting in theoutward direction O by a first rib 12.3 on the case 12 (not illustratedin FIGS. 12A to F, see FIGS. 5A to 8A) during about the second half ofits motion for needle extension.

The needle 4 is now fully inserted into the injection site asillustrated in FIGS. 6A and 6B. The time between the trigger button 13pressed and the needle 4 being fully inserted is very short, howeverseveral mechanical operations take place in this time. The needleextension depth is defined by the carrier 7 relative to the chassis 2not relative to the case 12, so if the user flinches or fails to holdthe auto-injector 1 hard against the skin, only the case 12 will move inthe distal direction D while the injection depth remains constant.

As soon as the plunger 9 has closed the gap to the stopper 6 under forceof the drive spring 8 the stopper 6 is pushed in the proximal directionP within the syringe 3 displacing the medicament M through the needle 4.

Immediately prior to the end of expelling the medicament with thestopper 6 having almost bottomed out in the syringe 3 as illustrated inFIGS. 7A and 7B a feedback component 28 is released. The stack up oftolerances, most notably due to the syringe 3 requires that the feedbackmust always be released prior to fully expelling the medicament.Otherwise, with certain combinations of parts, the feedback would notalways release. The feedback component 28 comprises an elongate portion28.1 arranged within the distal plunger sleeve 17 and a distal end plate28.2 arranged between the carrier end face 10 and an end face of thetrigger button 13. Two second resilient arms 30 originate from thedistal carrier end face 10 and extend in the proximal direction P. Afeedback spring 29 is arranged to bias the feedback component 28 in thedistal direction D relative to the carrier 7 by proximally bearingagainst a rib on the second resilient arms 30 and distally against thefeedback component 28 (not illustrated).

Note: the feedback component 28 is not illustrated in FIGS. 16A, B and Cfor clarity since it does not affect the function of the button releasemechanism 26. A feedback release mechanism 31 for releasing the feedbackcomponent 28 is schematically illustrated in FIGS. 14A, 14B and 14C.Referring now to FIG. 14A, the feedback release mechanism 31 comprisesthe second resilient arms 30. A ramped inward boss 30.1 is arranged oneach second resilient arm 30 which is engaged to a respective outwardeleventh ramp 28.3 on the elongate portion 28.1 of the feedbackcomponent 28 in such a manner that the second resilient arm 30 isdeflected in the outward direction O under load of the feedback spring29. In an initial state A of the feedback release mechanism 31 thesecond resilient arms 30 are prevented from being outwardly deflected byoutward support of the distal plunger sleeve 17 thus preventingtranslation of the feedback component 28 relative to the carrier 7. Thefeedback release mechanism 31 remains in state A until immediately priorto fully expelling the medicament with the stopper 6 having almostbottomed out in the syringe 3 as illustrated in FIGS. 7A and 7B. At thispoint the plunger 9 has been translated in the proximal direction Prelative to the carrier 7 to such an extent that the second resilientarms 30 are no longer supported by the distal plunger sleeve 17. Thefeedback release mechanism 31 has thus arrived in a state B illustratedin FIG. 14B. Due to the ramped engagement between the ramped inward boss30.1 and the outward eleventh ramp 28.3 the second resilient arm 30 isoutwardly deflected under load of the feedback spring 29 thusdisengaging the feedback component 28 from the carrier 7 and allowingthe feedback component 28 to move in the distal direction D driven bythe feedback spring 29 in a state C illustrated in FIG. 14C. Hence, thefeedback component 28 is accelerated in the distal direction D and thedistal end plate 28.2 impacts on the inside of the trigger button 13producing audible and tactile feedback to the user that expelling themedicament is about finished.

FIGS. 8A and 8B show the auto-injector 1 with the stopper 6 havingentirely bottomed out in the syringe 3.

As mentioned above the user is able to let the case 12 move by a fewmillimeters in the distal direction D under the force of the controlspring 19 without affecting the position of the needle 4 as long as thatmotion is below a predefined distance. If the user wishes to end theinjection, at any time, they must allow the case 12 to move in thedistal direction D beyond that distance. FIGS. 9A and 9B show theauto-injector 1 with the chassis extended, e.g. when lifted from theinjection site with the case 12 moved all the way in the distaldirection D so that the chassis 2 protrudes from the proximal end of thecase 12. As the case 12 is moved the first collar 20 releases thecarrier 7 and then the second collar 21 releases from the case 12 andpulls the carrier 7 in the distal direction D. The sequencing of thisswitching is critical as retraction will fail if both collars 20, 21 areattached to the carrier 7 at the same time. This is overcome byseparating the switching of the collars 20, 21 by a significantdisplacement of the case 12.

The switching of the first collar 20 is illustrated in FIGS. 12E and F.In FIG. 12E the case 12 has been allowed to move in the distal directionD under load of the control spring 19, e.g. during removal of theauto-injector 1 from the injection site. The first rib 12.3 (notillustrated, see FIG. 9A) is removed from outwardly behind the arrowhead20.1. The first collar 20 is still being pushed in the proximaldirection P by the control spring 19. Due to the engagement of theinward ninth ramp 20.3 on the arrowhead 20.1 with the distal tenth ramp7.6 on the carrier 7 the arrowhead 20.1 is deflected in the outwarddirection O into the aperture 2.5 of the chassis 2 (illustrated in FIGS.12A to 12F), the needle extension control mechanism 24 arriving in astate E as illustrated in FIG. 12E, decoupling the first collar 20 fromthe carrier 7 and latching it to the chassis 2.

As the case 12 is moving further in the distal direction D relative tothe chassis, e.g. on removal from the injection site, the syringeretraction control mechanism 25 switches from its state A (cf. FIG. 13A)into a state B illustrated in FIG. 13B. The case 12 and the secondcollar 21 locked to the case 12 move together in the distal direction Dwhile the carrier 7 is held in place by the detent mechanism 18 in itsstate C as described above (cf. FIG. 11C). Due to this motion the inwardboss 21.3 on the second beam head 21.2 of the proximal beam 21.1 on thesecond collar 21 no longer inwardly abuts the carrier 7. Instead theinward boss 21.3 is deflected in the inward direction I into a thirdrecess 7.7 in the carrier 7 due to the ramped engagement of the secondbeam head 21.1 to the ramped second case detent 12.2 under load of thecontrol spring 19. The syringe retraction control mechanism 25 thusarrives in a state C as illustrated in FIG. 13C with the second collar21 decoupled from the case 12 and coupled to the carrier 7. The detentmechanism 18 applies a small retarding force to the movement of thecarrier 7 before the syringe retraction control mechanism 25 switches tostate C as there is a small sliding force, applied by the second collar21, pulling the carrier 7 in the distal direction D on translation ofthe case 12 in the distal direction D when the needle extension controlmechanism 24 has already been switched into state E. If the carrier 7moves too far in the distal direction D before the second collar 21switches, the case 12 runs out of travel before the inward boss 21.3 candeflect into the third recess 7.7 preventing retraction.

Starting from the position C of the detent mechanism 18 (cf. FIG. 11C)the carrier 7 and hence the rhomboid ramp member 7.1 are translated inthe distal direction D under load of the control spring 19. Hence, thedistal fifth ramp 7.3 of the rhomboid ramp member 7.1 engages theproximal third ramp 2.3 on the first beam head 2.2 of the resilient beam2.1 in a manner deflecting the resilient beam 2.1 in the inwarddirection I. This applies the small retarding force to the movement ofthe carrier 7 required for ensuring the switching of the second collar21 to the carrier 7. The resilient beam 2.1 and the rhomboid ramp member7.1 are offset sideways to allow the resilient beam 2.1 to pass withoutcontacting the rhomboid ramp member 7.1 as soon as the first beam head2.2 is entirely inwardly from the ramp member 7.1 in a state Dillustrated in FIG. 11D.

The control spring 19 is grounded at its proximal end in the case by thefirst collar 20 being abutted against the chassis 2. The distal end ofthe control spring 19 moves the second collar 21 in the distal directionD taking with it the carrier 7 and hence the syringe 3 with the needle 4overcoming the detent mechanism 18 as illustrated in FIG. 11D. Note thatthe needle 4 is retracted by the auto-injector 1 as soon as the userallows the case 12 to translate sufficiently far as opposed toauto-injectors with needle shields which require the user to remove theauto-injector from the injection site thereby themselves pulling theneedle out of the skin for allowing the needle shield to advance.

As the movement allowed of the feedback component 28 is limited relativeto the carrier 7 it is no longer in contact with the trigger button 13which has moved in the distal direction D with the case 12 on removalfrom the injection site.

When the retraction begins the feedback spring 29 does not provide anyretarding force. Once the feedback component 28 hits the trigger button13 again on retraction of the carrier 7 the feedback spring 29 must berecompressed, reducing the force driving the final part of retraction.In order to ensure a reliable retraction despite this reducing force thecontrol spring 19 must be appropriately dimensioned.

The retraction ends when the distal collar 21 meets a first back stop12.4 on the case 12 as in FIGS. 10A and 10B. The arrowhead 20.1 on thefirst collar 20 is inwardly supported by the carrier 7 in a state Fillustrated in FIG. 12F and thus prevented from deflecting in the inwarddirection I. The outward sixth ramp 20.2 of the arrowhead 20.1 isengaged behind the first rib 12.3 on the case 12 preventing the case 12from being pushed in the proximal direction P again. A clearance may beprovided between the arrowhead 20.1 and the first rib 12.3 to allow fortolerances.

The detent mechanism 18 returns to state A as in FIG. 11A locking thecarrier 7 in position relative to the chassis 2 as it did initially,however it cannot be unlocked now as the case 12 cannot move relative tothe chassis 2.

A tab 20.4 on the first collar 20 is now visible through an indicatorwindow 32 in the case 12—indicating the auto-injector 1 has been used.

FIG. 17 is an isometric view of an alternative embodiment of the plungerrelease mechanism 27. The plunger release mechanism 27 prevents movementof the plunger 9 in the proximal direction P relative to the carrier 7until the carrier 7 is moved in the proximal direction P for needleextension. As opposed to the plunger release mechanism 27 of FIG. 15,where relative movement of the carrier 7 and trigger button 13 are usedto trigger the release of the plunger 9, the alternative embodiment ofFIG. 17 releases the plunger 9 by movement of the carrier 7 relative tothe second collar 21. FIG. 17 illustrates the plunger release mechanism27 prior to plunger release. The second collar 21 is shown transparentto improve clarity. The plunger 9 is being pushed in the proximaldirection P by the drive spring 8. In order for the plunger 9 toadvance, it must rotate around a twelfth ramp 7.8 on the carrier 7. Aramp member 9.1 on the plunger 9 is arranged to engage this twelfth ramp7.8. Rotation of the ramp member 9.1 is blocked by an inwardlongitudinal rib 21.5 on the second collar 21 splined in a longitudinalaperture 7.9 in the carrier 7. The case 12 and the second collar 21remain in the same position, i.e. coupled to each other for joint axialtranslation. On depression of the trigger button 13 the carrier 13 andthe plunger 9 being part of the drive sub-assembly are moved in theproximal direction P, first by the user pressing the trigger button 13and then by the control spring 19 taking over via the first collar 20 asdescribed above. Once the carrier 7 moves sufficiently far in theproximal direction P relative to the second collar 21 the ramp member9.1 on the collar 9 comes clear of the longitudinal rib 21.5 on thesecond collar 21 and can rotate past the proximal end of thelongitudinal rib 21.5 due to its ramped engagement to the twelfth ramp7.8 under load of the drive spring 8. Hence, the drive spring 8 advancesthe plunger 9 in the proximal direction P for expelling the medicamentM.

FIG. 18 is a longitudinal section of an alternative embodiment of thebutton release mechanism 26. Other than the button release mechanism 26of FIG. 16 which gives the appearance of a revealing trigger button 13on skin contact by switching the ground of the trigger button 13 betweenthe carrier 7 and the case 12, the button release mechanism 26 of FIG.18 starts with the trigger button 13 locked but protruding from thedistal end of the case 12. Once the carrier 7 has moved in the distaldirection D on skin contact of the chassis 2, it is possible to depressthe trigger button 13 and activate the auto-injector 1. This ensures asequenced operation.

In the embodiment of FIG. 18 the trigger button 13 has two proximalbeams 13.1, each of them having a ramped outward boss 13.4. In theinitial state shown in FIG. 18 the ramped outward bosses 13.4 areengaged in respective fourth recesses 12.5 in the case 12. Disengagingthe ramped outward bosses 13.4 from the fourth recesses 12.5 isprevented by the carrier 7 inwardly supporting the proximal beams 13.1in a manner to keep the proximal beams 13.1 from deflecting inwardly.Inward protrusions 13.5 on the proximal beams 13.1 abut against a secondrib 7.10 on the carrier 7 in a manner preventing the carrier 7 frommoving further in the proximal direction P in the initial state. Oncethe carrier 7 has moved in the distal direction D on skin contact of thechassis 2 a first window 7.11 in the carrier 7 is moved behind theinward protrusion 13.5 so as to allow the proximal beams 13.1 to beinwardly deflected due to their ramped engagement in the fourth recesses12.5 on depression of the trigger button 13. The proximal beams 13.1 arenow outwardly supported by the case 12 and remain engaged to the carrier7 even on retraction of the needle 4. The trigger button 13 doestherefore not return to its initial position, indicating that theauto-injector 1 has been used.

The button release mechanism 26 illustrated in FIG. 18 may preferably becombined with the plunger release mechanism 27 illustrated in FIG. 17.

FIGS. 19A and 19B show two longitudinal sections of an alternativeembodiment of the detent mechanism 18. The detent mechanism 18 of FIGS.11A to 11D, which may be referred to as a “race track” mechanism becauseof the first beam head 2.2 travelling around the rhomboid ramp member7.1 has multiple functions which control the movement of the carrier 7relative to the chassis 2. The alternative detent mechanism 18 of FIGS.19A and 19B uses three clips 7.12, 7.13, 2.6 to produce the same effect.

The first clip 7.12 is arranged as an outwardly biased resilient beam onthe carrier 7 extending from the carrier 7 in the proximal direction P.the first clip 7.12 is arranged to prevent the carrier 7 from beingmoved in the proximal direction P prior to the chassis 2 being depressedor rather the case 12 being translated on skin contact. The first clip7.12 is composed of two sections side by side. A first section 7.14prevents movement of the carrier 7 in the proximal direction P byabutting the chassis 2 in a recess. A second section 7.15 is arranged asan outwardly protruding clip head arranged to be ramped inwards by aramp feature 12.6 on the chassis 12 for releasing the first clip 7.12thereby unlocking the carrier 7 from the chassis 2 when the case 12 isbeing translated in the proximal direction P on skin contact. Alongitudinal slot 2.7 in the chassis 2 is arranged for allowing thesecond section 7.15 to slide in the proximal direction P once the lockhas been released. A slight friction force between the first clip 7.12and the chassis 2 provides the retarding force required to ensureretraction.

The second clip 7.13 is arranged as a resilient beam on the carrier 7extending in the distal direction D having an outwardly protruding thirdbeam head 7.16 with a proximal ramp. The third beam head 7.16 serves asa back stop against a third rib 2.9 on the chassis 2 for preventing thecarrier 7 moving in the distal direction D from its initial position.The carrier 7 and chassis 2 are assembled with the second clip 7.13 inthis position prior to inserting the syringe 3 into the carrier 7 whichis facilitated by the proximal ramp on the third beam head 7.16. Thesyringe 3 locks the clip in place by preventing inward deflection thuscreating a fixed stop.

The third clip 2.6 is a resilient beam on the chassis 2 extending in thedistal direction D. A ramped fourth beam head 2.8 on the third clip 2.6is arranged to inwardly engage in a fifth recess 7.17 in the carrier 7.Once the first clip 7.12 is unlocked, the user can load the third clip2.6 by pressing the carrier 7 in the proximal direction P on depressionof the trigger button 13. The third clip 2.6 is loaded in compression,i.e. it will bend outwards and release suddenly due to its rampedengagement to the carrier 7 providing the detent functionality similarto that illustrated in FIG. 11B.

FIG. 20 is a longitudinal section of a third embodiment of the detentmechanism 18 which is a variation on the embodiment of FIGS. 19A and19B. In this embodiment the detent function of the third clip 2.6 hasbeen added into the first clip 7.12. The lock between the case 12 andthe carrier 7 is released in the same way, but the detent is provided bydeflecting the first clip 7.12 inwards a second level which is achievedby the chassis 2 not having a slot 2.7 for the second section 7.15.Instead the second section 7.15, once ramped inwards by the ramp feature12.6 on the case 12 has to be further ramped inwards inside the chassis2 on axial load between the chassis 2 and the carrier 7, suddenlyreleasing their engagement.

FIG. 21 is a longitudinal section of an alternative embodiment of thefeedback release mechanism 31. As opposed to the feedback releasemechanism 31 of FIG. 14 where the feedback spring 29 acts between thecarrier 7 and the feedback component 28, in the embodiment illustratedin FIG. 21 the feedback spring 29 acts between the case 12 and thefeedback component 28. During needle extension the feedback spring 29 iscompressed as the feedback component 28 moves with the carrier 7relative to the case 12. When the feedback component 28 is released bythe plunger 9 shortly before the end of dose, the feedback component 28moves in the distal direction D and impacts the trigger button 13. Otherthan in FIG. 14 the feedback spring 29 is not being recompressed duringneedle retraction since it is grounded in the case 12 not in the carrier7.

FIGS. 22A and 22B show longitudinal sections of an alternativeembodiment of the needle extension control mechanism 24 which is alsoarranged to perform the detent function of the detent mechanism 18 onneedle retraction and needle extension. FIG. 23 shows a correspondingisometric view. A fourth clip 20.5 on the first collar 20 is arranged asa resilient beam with a beam head having an inward proximal thirteenthramp 20.6 for engaging a fourth rib 7.18 on the carrier 7 and outwardlysupported by the case 12 so as to keep the first collar 20 engaged tothe carrier 7 prior to use, during needle extension and during expellingthe medicament. When the case 12 moves in distal direction relative tothe carrier, e.g. when the user lifts the case 12 away from theinjection site at the end of injection, a sixth recess 12.7 in the case12 is moved outwardly behind the fourth clip 20.5 allowing the fourthclip 20.5 to release when the carrier 7 is pulled in the distaldirection D by the second collar 21. Since the fourth clip 20.5 has tobe ramped outwards a small force is required to release the fourth clip20.5, providing the retraction detent.

A fifth clip 2.10 on the chassis 2 abuts a block 20.7 on the firstcollar 20 prior to use preventing the first collar 20 and hence thecarrier 7 engaged to the first collar 20 from moving in the proximaldirection P. In order to release, the fifth clip 2.10 must be deflectedoutwards and over the block 20.7. Outward deflection of the fifth clip2.10 is initially prevented by the case 12. Once the case 12 has movedon skin contact a second window 12.8 in the case 12 appears outwardlyfrom the fifth clip 2.10 allowing outward deflection. The fifth clip2.10 is then deflected by a fourteenth ramp 7.19 on the carrier 7 whenthe carrier 7 is pushed in the proximal direction P on button depressionas the fourth clip 20.5 does allow translation of the carrier 7 in theproximal direction P relative to the first collar 20 but not the otherway round. The detent for needle extension is provided by having todeflect the fifth clip 2.10 when it is loaded by the control spring 19.

FIGS. 24A and 24B show longitudinal sections of a third embodiment ofthe needle extension control mechanism 24, also arranged to perform thefunctions of the detent mechanism 18. FIG. 25 is an isometric view ofthe needle extension control mechanism 24 of FIG. 24. The embodiment issimilar to that illustrated in FIGS. 22A, 22B and 23. The difference isthat the fifth clip 2.10 is arranged on the first collar 20 and theblock 20.7 is arranged on the chassis 2, i.e. their position has beenswitched, so there are two clips 2.10 and 20.5 on the first collar 20.

The fourth clip 20.5 is identical to that in FIG. 22B. It keeps thefirst collar 20 connected to the carrier 7 until the needle retractionis triggered, ensuring full needle extension length or depth is reachedand maintained until the retraction cycle is initiated by displacing thecase backwards in distal direction relative to the chassis, e.g. whenremoving the auto-injector 1 from the skin.

The fifth clip 2.10 provides the detent for needle extension andreleases the first collar 20 from the chassis 2, initiating needleextension. The fifth clip 2.10 prevents the first collar 20 and hencethe carrier 7 engaged to the first collar 20 from moving in the proximaldirection P prior to use by abutting the block 20.7 on the chassis 2. Inorder to release, the fifth clip 2.10 must be deflected outwards andover the block 20.7. Outward deflection of the fifth clip 2.10 isinitially prevented by the case 12. Once the case 12 has moved on skincontact the second window 12.8 in the case 12 appears outwardly from thefifth clip 2.10 allowing outward deflection. The fifth clip 2.10 is thendeflected by the fourteenth ramp 7.19 on the carrier 7 when the carrier7 is pushed in the proximal direction P on button depression as thefourth clip 20.5 does allow translation of the carrier 7 in the proximaldirection P relative to the first collar 20 but not the other way round.The detent for needle extension is provided by having to deflect thefifth clip 2.10 when it is loaded by the control spring 19.

FIGS. 26A and 26B show a longitudinal section of a third embodiment ofthe feedback release mechanism 31. This embodiment works without theneed for a dedicated feedback spring. The plunger 9 comprises aproximally ramped rib 9.2 arranged to splay two seventh clips 7.21 onthe carrier 7 immediately prior to the end of dose. When the proximallyramped rib 9.2 has travelled past the seventh clips 7.21 they snap backand impact the plunger 9 generating a sound. The tubular shape of thecarrier 7 helps to transmit the sound. FIG. 26A shows the feedbackrelease mechanism 31 before release. FIG. 26B shows the feedback releasemechanism 31 after release. Proximal faces of the seventh clips 7.21 onthe carrier 7 are axially offset to facilitate assembly by lifting theseventh clips 7.21 over the distal side of the proximally ramped rib 9.2one by one.

FIGS. 27A and 27B show longitudinal sections of another embodiment ofthe auto-injector 1 in different section planes, the different sectionplanes approximately 90° rotated to each other, wherein theauto-injector 1 is in an initial state prior to use. The auto-injector 1is essentially identical to the one described in FIGS. 1 to 16. However,other than the auto-injector of FIGS. 1 to 16 the auto-injector 1 ofthis embodiment has a wrap-over sleeve trigger instead of a triggerbutton.

The wrap-over sleeve trigger 12 is the same component as the case 12which has a closed distal end face 12.10 other than the one in FIGS. 1to 16. An internal trigger button 13 is arranged at the distal endinside the sleeve trigger 12. Other than in FIGS. 1 to 16 the triggerbutton 13 is not visible nor does it protrude from the case 12 in anystate. In the initial state a clearance 33 is provided between thedistal end face 12.10 of the sleeve trigger 12 and the internal triggerbutton 13 allowing for some travel of the sleeve trigger 12 withoutinterfering with the trigger button 13.

As the auto-injector 1 does not differ from the auto-injector of FIGS. 1to 16 in other respects it is essentially operated in the same way withthe following exceptions:

As the chassis 2 is placed against the injection site the sleeve trigger12 translates in the proximal direction P relative to the chassis 2 intothe advanced position in a first phase of sleeve travel removing theclearance 33 between the distal end face 12.10 of the sleeve trigger 12and the internal trigger button 13. As in the embodiment of FIGS. 1 to16 this motion unlocks the detent mechanism 18 and the trigger button13. As the user continues to depress the sleeve trigger 12 in a secondphase of sleeve travel thereby further advancing it in the proximaldirection P the distal end face 12.10 hits the internal trigger button13 thereby depressing it until the first collar 20 is released from thechassis 2 and the control spring force is coupled on to the carrier 7.The carrier 7 then advances until the internal trigger button 13 stopson another rib in the case 12 and the plunger release mechanism 27 isreleased (note the peg 14 is shorter in this embodiment.

From a user perspective, the detent mechanism 18 is arranged to providea resistive force when the user reaches the second phase of sleevetravel. Internally, there is no difference to the embodiment of FIGS. 1to 16 at this point.

Needle extension is triggered by the user fully advancing the sleevetrigger 12 in the second phase of sleeve travel thereby fully depressingthe internal trigger button 13 and overcoming the detent mechanism as inthe embodiment of FIGS. 1 to 16.

As the control spring 19 takes over on button depression fully advancingthe carrier 7 for needle extension the internal trigger button 13bottoms out on an internal fifth rib 12.11 in the sleeve trigger 12 andthe internal trigger button 13 switches back to being locked to thesleeve trigger 12 as in FIG. 16C.

The embodiment of FIGS. 27A and 27B may also be combined with thealternative features illustrated in FIGS. 17 to 26.

It goes without saying that in all ramped engagements between twocomponents described in the above embodiments there may be just one rampon one or the other component or there may be ramps on both componentswithout significantly influencing the effect of the ramped engagement.

The invention claimed is:
 1. An auto-injector for administering a doseof a liquid medicament (M), comprising: a tubular chassis telescopablein a tubular case, a carrier subassembly comprising a tubular carrierslidably arranged relative to the chassis inside the case, the carrieradapted to contain a syringe with a hollow injection needle, a drivespring and a plunger for forwarding load of the drive spring to astopper of the syringe, wherein the syringe is lockable for joint axialtranslation with the carrier, a trigger button arranged distally orlaterally in or on the case, a control spring arranged around thecarrier, a needle extension control mechanism for coupling a proximalend of the control spring to either the carrier for advancing it forneedle extension or to the chassis for needle retraction depending onthe relative axial position of the carrier and the chassis, a plungerrelease mechanism arranged for releasing the plunger for expelling themedicament when the carrier has at least almost reached an extendedproximal position, a detent mechanism arranged for coupling the chassisto the carrier for joint axial translation relative to the case, whereinthe detent mechanism is arranged to decouple the chassis from thecarrier upon actuation of the trigger button thus allowing the carrierto move relative to the chassis so as to cause the needle extensioncontrol mechanism to switch the proximal end of the control spring tothe carrier for needle extension, a syringe retraction control mechanismarranged for coupling a distal end of the control spring to either thecarrier for needle retraction or to the case otherwise.
 2. Theauto-injector according to claim 1, characterized in that the needleextension control mechanism comprises a first collar biased by thecontrol spring in a proximal direction (P), wherein at least oneresilient beam is proximally arranged on the first collar, whereinrespective recesses are arranged in the carrier and case, wherein atransversal extension of a head of the resilient beam is wider than agap between the carrier and the chassis causing the head of theresilient beam to abut a distal face on the recess in the chassis whilebeing prevented from deflecting in an inward direction (I) by thecarrier or to abut a distal face on the recess in the carrier whilebeing prevented from deflecting in an outward direction (O) by thechassis thereby forwarding load from the control spring to the carrierfor needle extension, wherein the resilient beam is arranged to beswitched between the chassis and the carrier by ramped engagement of thehead to the distal faces under load of the control spring depending onthe relative longitudinal position between the chassis and the carrier.3. The auto-injector according claim 1, characterized in that theplunger release mechanism comprises at least one resilient arm on thecarrier arranged to be in a ramped engagement to the plunger so as todisengage them under load of the drive spring, wherein a peg protrudesfrom a distal end face of the trigger button in the proximal direction(P) in a manner to support the resilient arm preventing disengagement ofthe carrier from the plunger and thus release of the drive spring whenthe carrier is in a distal position, wherein the trigger button isarranged to remain in position relative to the case when the carrier istranslated for advancing the needle so as to pull the resilient arm awayfrom the peg thus allowing deflection of the resilient arm due to theramped engagement under load of the drive spring for disengaging theplunger from the carrier and releasing the drive spring for movement ofthe plunger when the carrier has reached a predefined position relativeto the case.
 4. The auto-injector according to claim 1, characterized inthat the detent mechanism is arranged to provide a resistive force whichhas to be overcome to advance the carrier in the proximal direction (P)for needle extension.
 5. The auto-injector according to claim 1,characterized in that the detent mechanism is arranged to provide aresistive force resisting translation of the carrier in the distaldirection (D) relative to the chassis for keeping the carrier in adefined position in a transitional state with both ends of the controlspring decoupled from the carrier.
 6. The auto-injector according toclaim 4, characterized in that the detent mechanism comprises aresilient beam on the chassis and a rhomboid ramp member on the carrier,the resilient beam being essentially straight when relaxed and having afirst beam head arranged to interact in a ramped engagement with aproximal fourth ramp or a distal fifth ramp on the rhomboid ramp memberin such a manner that application of a translative force on the carrierrelative to the chassis in the proximal direction (P) with the firstbeam head engaged to the fourth ramp deflects the resilient beam in onetransversal direction (O, I) when a predetermined value of thetranslative force, at least depending on the resilience of the resilientbeam, is overcome so as to allow the first beam head to travel along onetransversal side of the rhomboid ramp member on continued relativetranslation of the components, wherein the resilient beam is allowed torelax when the first beam head has reached the fifth ramp therebyengaging it in a manner that application of a translative force on thecarrier (in the distal direction (D) deflects the resilient beam in theother transversal direction (I, O) when a predetermined value of thetranslative force, at least depending on the resilience of the resilientbeam, is overcome so as to allow the first beam head to travel along theother transversal side of the rhomboid ramp member on continuedtranslation of the carrier.
 7. The auto-injector according to claim 1,characterized in that the case is arranged to lock the detent mechanismprior to being translated in the proximal direction (P) relative to thechassis when the chassis is being pressed against an injection site,wherein the case when translated into an advanced position in theproximal direction (P) is arranged to unlock the detent mechanismrendering it operable.
 8. The auto-injector according to claim 1,characterized in that the trigger button is arranged distally and is atleast initially coupled to the carrier, wherein the case is arranged toabut the trigger button in the initial state preventing depression ofthe trigger button, wherein on translation of the case into the advancedposition when the chassis is being pressed against the injection sitethe trigger button remains coupled to the carrier thus emerging from thecase so as to allow depression for starting an injection cycle.
 9. Theauto-injector according to claim 1, characterized in that the syringeretraction control mechanism comprises a second collar bearing againstthe distal end of the control spring and having a resilient proximalbeam with a second beam head having an inward boss, wherein the secondbeam head is arranged to be in a ramped engagement with a second casedetent in the case in a manner ramping the second beam head in theinward direction (I) under load of the control spring in the distaldirection (D), wherein the inward boss is arranged to inwardly abut thecarrier for preventing inward deflection of the second beam head andkeep the second collar locked to the case, wherein a third recess isarranged in the carrier for allowing the inward boss to be inwardlydeflected on translation of the case in the distal direction (D)relative to the carrier on removal of the auto-injector from theinjection site.
 10. The auto-injector according to claim 1,characterized in that the trigger button is arranged distally, whereinthe case is arranged as a wrap-over sleeve trigger having a closeddistal end face covering the trigger button, wherein in an initial statea clearance is provided between the distal end face of the sleevetrigger and the trigger button allowing for some travel of the sleevetrigger against the bias of the control spring in the proximal direction(P) in a first phase before abutting the trigger button.
 11. Theauto-injector according to claim 1, characterized in that a releasablefeedback component is provided, capable of, upon release, generating anaudible and/or tactile feedback to a user, wherein the feedbackcomponent is arranged to be released when the plunger reaches a positionrelative to the syringe in which the stopper is located in proximity ofa proximal end of the syringe, and wherein the released feedbackcomponent impacts on a housing component indicating the end of theinjection.
 12. The auto-injector according to claim 2, characterized inthat a visual use indicator is provided, comprising at least oneindicator window in the case, wherein a part of the chassis is arrangedto be located behind the indicator window when the case is in its distalposition biased by the control spring, wherein a tab on the first collaris located outwardly from the part of the chassis after the collar hasbeen translated in the proximal direction (P) during needle extension,wherein the tab and the part of the chassis exhibit a visuallydistinctive feature.
 13. A method of operating an auto-injector, theauto-injector comprising: a tubular chassis telescopable in a tubularcase, a carrier subassembly comprising a tubular carrier slidablyarranged relative to the chassis inside the case, the carrier adapted tocontain a syringe with a hollow injection needle, a drive spring and aplunger for forwarding load of the drive spring to a stopper of thesyringe, wherein the syringe is lockable for joint axial translationwith the carrier, a trigger button arranged distally or laterally in oron the case, a control spring arranged around the carrier, a needleextension control mechanism for coupling a proximal end of the controlspring to either the carrier or to the chassis, a plunger releasemechanism arranged for locking the drive spring, a detent mechanismarranged for coupling the chassis to the carrier, a syringe retractioncontrol mechanism arranged for coupling a distal end of the controlspring to either the carrier or to the case, the method comprising thesteps of: coupling the proximal end of the control spring to the carrierby the needle extension control mechanism, preventing release of thedrive spring by the plunger release mechanism, preventing decoupling ofthe chassis from the carrier by the detent mechanism and coupling thedistal end of the control spring to the case by the syringe retractioncontrol mechanism in an initial state, translating the case in theproximal direction (P) relative to the chassis against the force of thecontrol spring, unlocking the detent mechanism when the case istranslated into an advanced position thereby allowing translation of thecarrier relative to the chassis, translating the carrier in the proximaldirection (P) thereby switching the needle extension control mechanismso as to decouple the proximal end of the control spring from thechassis and couple it to the carrier, thereby releasing the controlspring for advancing the carrier for needle extension, releasing thedrive spring by the plunger release mechanism when the needle at leastalmost reaches an extended proximal position thereby allowing the drivespring to advance the plunger and the stopper for at least partiallyexpelling the medicament (M), translating the case in the distaldirection (D) under load of the control spring relative to the carrier ,decoupling the proximal end of the control spring from the carrier andcoupling it to the chassis by the needle extension control mechanism anddecoupling the distal end of the control spring from the case andcoupling it to the carrier by the syringe retraction control mechanismwhen the case reaches a defined position relative to the carrier duringtranslation in the distal direction (D), retracting the carriersubassembly into the chassis into a needle safe position under load ofthe control spring.
 14. The method according to claim 13, characterizedin that a resistive force is provided by the detent mechanism which hasto be overcome to advance the carrier in the proximal direction (P) forneedle extension.
 15. The method according to claim 13, characterized inthat a resistive force is provided by the detent mechanism resistingtranslation of the carrier in the distal direction (D) relative to thechassis for keeping the carrier in a defined position after decouplingthe proximal end of the control spring from the carrier and coupling itto the chassis by the needle extension control mechanism and beforedecoupling the distal end of the control spring from the case andcoupling it to the carrier by the syringe retraction control mechanism.